Efficacy and safety of Shengxian Yixin Granule for treating heart failure with preserved ejection fraction: a study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) is a highly complex clinical syndrome associated with significant morbidity and mortality. Its underlying mechanisms are poorly understood, treatment options are limited, the disease burden on patients is substantial, and clinical outcomes are poor. Previous clinical studies have preliminarily suggested that Shengxian Yixin Granule (SXYX) is an effective herbal formula for the treatment of HFpEF, but it lacks high-quality clinical evidence. This study therefore plans to conduct a randomized controlled trial (RCT) to evaluate the efficacy and safety of SXYX in treating HFpEF, aiming to provide a new therapeutic strategy for this condition. METHODS: This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. It will be conducted at four Chinese medicine hospitals in China. A total of 148 eligible patients with HFpEF will be enrolled and randomly assigned in a 1:1 ratio to the SXYX group or the placebo group. The SXYX group will receive Shengxian Yixin Granule, while the placebo group will receive a matching placebo. Both groups will receive standard Western medical therapy as background treatment. The treatment duration for all groups is 24 weeks. The primary outcome is the change in peak VO2 (assessed by cardiopulmonary exercise testing) from baseline to 24 weeks. Secondary outcome measures include the change in peak oxygen uptake from baseline to 12 weeks, NT-proBNP, echocardiographic parameters, NYHA functional class, 6-minute walk test distance (6MWT), Traditional Chinese Medicine (TCM) syndrome scale, major symptoms and signs, EQ-5D score, and coagulation function. These outcomes will be used to evaluate the efficacy of SXYX. Routine blood, urine, and stool tests, liver and kidney function tests, electrocardiograms, and adverse events will be used to assess the safety of SXYX. Wearable monitoring devices will be used for out-of-hospital, dynamic, and multidimensional assessment of patients' exercise tolerance, including heart rate, blood oxygen saturation, step count, and walking distance. DISCUSSION: This study will evaluate the efficacy and safety of SXYX in treating HFpEF. The findings will provide a scientific basis for the clinical application of SXYX. CLINICAL TRIAL REGISTRATION: https://itmctr.ccebtcm.org.cn, identifier ITMCTR2026000833.